Transcript Slide 1

Asymmetric Frontiers in Lanthanide Catalysis
Andrew Lohse
Hsung Group
University of Wisconsin – Madison
December 11, 2008
Overview
• Background/Fundamentals
• Asymmetric Cycloadditions
• Multifunctional Asymmetric Catalysts
• C-C Bond Formation
• C-P Bond Formation
• C-O Bond Formation
• Conclusions/Future Directions
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Location
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The Lanthanide Contraction
Mikami, K.; Terada, M.; Matsuzawa, H. Angew. Chem., Int. Ed. 2002, 41, 3554.
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Contracted Nature of the f-Orbitals
• Shielded by 5s and 5p
– Unavailable for bonding
• Lack of orbital restrictions
– No ligand field effects
– Sterically saturated
• Ionic character
– “Hard” Lewis acids
– Oxophilic
“triple-positively charged closed shell inert gas electron cloud”
http://int.ch.liv.ac.uk/Lanthanide/Lanthanides.html
Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed; Springer-Verlag: Berlin, 1999.
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Well-Known Examples in Synthesis
Luche Reduction
Evans-Tischenko Reduction
Oxidative PMB Deprotection
Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226. Evans, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990, 112, 6447.
Green, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; John Wiley & Sons: New York, 1999.
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Why Use Lanthanides as Catalysts?
• Variation of Size/Lewis Acidity
Tunability
• Nature of f orbitals
–ionic character
–high coordination #s
• NMR Analysis
–Diamagnetic: La3+, Ce4+, Yb2+, Lu3+
–Paramagnetic: Pr3+, Sm2+/3+, Eu3+
• Water/Air stable
• Recyclable
Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 4th ed; Wiley Interscience: New York, 2005.
Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed; Springer-Verlag: Berlin, 1999.
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Aqueous Aldol
• Use of ambient temperature
• Less rigorous conditions
• Recyclable
Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96, 7503.
Kobayashi, S. Chem. Lett. 1991, 2187.
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Historical Perspective
Parker, D. Chem. Rev. 1991, 91, 1441.
Aspinall, H. C. Chemistry of the f-Block Elements; Gordon and Breach: Amsterdam , 2001.
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Asymmetric Hetero-Diels-Alder
Bednarski, M.; Maring, C.; Danishefsky, S. Tetrahedron Lett. 1983, 24, 3451.
Mikami, K.; Terada, M.; Matsuzawa, H. Angew. Chem., Int. Ed. 2002, 41, 3554.
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Aza-Diels-Alder
Kobayashi, S.; Ishitani, H., Araki, M.; Hachiya, I. Tetrahedron Lett. 1994, 35, 6325.
Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed; Springer-Verlag: Berlin, 1999.
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Proposed Transition State
• First catalytic asymmetric
aza-Diels-Alder
• Lewis acid activation of diene
• Catalyst not poisoned by
nitrogen functionality
Kobayashi, S.; Ishitani, H., Araki, M.; Hachiya, I. Tetrahedron Lett. 1994, 35, 6325.
Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed; Springer-Verlag: Berlin, 1999.
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1,3-Dipolar Cycloaddition
Sanchez-Blanco, A. I.; Gothelf, K. V.; Jørgensen, K. A. Tetrahedron Lett. 1997, 38, 7923.
Kobayashi, S.; Kawamura, M. J. Am. Chem. Soc. 1999, 120, 5840.
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Overview
• Historical Perspective
• Asymmetric Cycloadditions
• Multifunctional Asymmetric Catalysts
• C-C Bond Formation
• C-P Bond Formation
• C-O Bond Formation
• Conclusions/Future Directions
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Concept of Multifunctional Catalysis
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Shibasaki, M.; Kanai, M.; Matsunaga, S. Aldrichim. Acta 2006, 39, 31.
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Preparation of Catalysts
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Shibasaki, M.; Kanai, M.; Matsunaga, S. Aldrichim. Acta 2006, 39, 31.
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Asymmetric Nitro-Aldol
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Sasai, H.; Suzuki, T.; Itoh, N.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992, 114, 4418.
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Postulated Catalytic Cycle
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Sasai, H.; Suzuki, T.; Itoh, N.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992, 114, 4418.
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Tunability of Ln3+ Ionic Radius
• 1st systematic study of its kind
• Small changes (0.1 Å) cause
drastic differences
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Sasai, H.; Suzuki, T.; Itoh, N.; Arai, S.; Shibasaki, M. Tetrahedron Lett. 1993, 34, 2657.
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Concept of Direct Aldol Reaction
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
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Direct Aldol Reaction
• Long reaction times
• Excess amounts of ketone
• High catalyst loading
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
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A Heteropolymetallic Catalyst
• KOH formed in situ
• Use of (R)-LPB ineffective
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
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Mechanistic Insights
• kH/kD ~ 5 with d3-acetophenone
• Rate independent of aldehyde
• Coordination of aldehyde to La3+
confirmed by NMR studies
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
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Application in Total Synthesis
Yoshikawa, N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 4168.
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Michael Addition of Malonates
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194.
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Postulated Catalytic Cycle
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194.
Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed; Springer-Verlag: Berlin, 1999.
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Enantiofacial Control
pro-(R)
Favored
pro-(S)
Disfavored
+ 4.9 kcal/mol
(UFF)
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194.
Rappé, A. K.; Casewit, C. J.; Colwell, K. S.; Goddard III, W. A.; Skiff, W. M. J. Am. Chem. Soc. 1995, 114, 10024.
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NMR Studies
Why LSB vs. LLB?
• No coordination with LLB
• Size of coordination sphere
• LSB activates enone and
controls its direction
• Difference in dihedral angles
of BINOL ligands
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194.
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
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Tunability of Alkali Metal
Michael Addition
Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194.
Shibasaki, M.; Sasai, H.; Arai, T.; Iida, T. Pure & Appl. Chem. 1998, 70, 1027.
Nitro-Aldol
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Improved Catalyst
Kim, Y. S.; Matsunaga, S.; Das, J.; Sekine, A.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 6506.
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Overview
• Historical Perspective
• Asymmetric Cycloadditions
• Multifunctional Asymmetric Catalysts
• C-C Bond Formation
• C-P Bond Formation
• C-O Bond Formation
• Conclusions/Future Directions
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Hydrophosphonylation of Imines
Sasai, H.; Arai, S.; Tahara, Y.; Shibasaki, M. J. Org. Chem. 1995, 60, 6656.
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
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Hydrophosphonylation of Imines
Gröger, H.; Saida, Y.; Sasai, H.; Yamaguchi, K.; Martens, J.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 3089.
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
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Effectiveness of Cyclic Phosphites
Maffei, M.; Buono, G. Tetrahedron 2003, 59, 8821.
Schlemminger, I.; Saida, Y.; Gröger, H.; Maison, W.; Durot, N.; Sasai, H.; Shibasaki, M.; Martens, J. J. Org. Chem. 2000, 65, 4818.
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Proposed Catalytic Cycle
Gröger, H.; Saida, Y.; Sasai, H.; Yamaguchi, K.; Martens, J.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 3089.
Schlemminger, I.; Saida, Y.; Gröger, H.; Maison, W.; Durot, N.; Sasai, H.; Shibasaki, M.; Martens, J. J. Org. Chem. 2000, 65, 4818.
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Overview
• Historical Perspective
• Asymmetric Cycloadditions
• Multifunctional Asymmetric Catalysts
• C-C Bond Formation
• C-P Bond Formation
• C-O Bond Formation
• Conclusions/Future Directions
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Epoxidation of Enones
Nemoto, T.; Ohshima, T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 2725.
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Postulated Catalytic Cycle
Nemoto, T.; Ohshima, T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 2725.
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Diversity in Catalysis
Shibasaki, M.; Sasai, H.; Arai, T.; Iida, T. Pure & Appl. Chem. 1998, 70, 1027.
Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
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Conclusions
• Advantages of lanthanide catalysis
‒ Tunability
‒ Diversity of possible reactions
‒ Water/air stable
‒ Recyclable
• Limitations
‒ Long reaction times
‒ High catalyst loading
‒ Aggregation of complexes
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Future Directions
• Increase efficiency of catalysts
• Application in industry
• Broaden the scope of substrates
“These elements perplex us in our researches, baffle us in our
speculations, and haunt us in our very dreams. They stretch like
an unknown sea before us; mocking, mystifying and murmuring
strange revelations and possibilities.”
- Sir William Crookes (1887)
Address to the Royal Society
Aspinall, H. C. Chemistry of the f-Block Elements; Gordon and Breach: Amsterdam , 2001.
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Acknowledgements
• Professor Richard Hsung
• Hsung group members
• Practice talk attendees
- John Feltenberger
- Kyle DeKorver
- Brittland DeKorver
- Lauren Carlson
- Jenny Werness
- Aaron Almeida
- Kevin Williamson
- Dr. Yu Zhang
- Dr. Ryuji Hayashi
- Dr. Yu Tang
- Ting Lu
- Gang Li
- Grant Buchanan
- Yonggang Wei
- Hongyan Li
• Kat Myhre
• Colleen Lohse
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